We plan to extend our work on the regulation of the lactose operon to the galactose operon of E. coli and to the glucocorticosteroid induced killing of cells of the immune system. (1) The Lactose Operon: The structure of the repressor, its conformational changes, and the geometry of the repressor-operator complex will be examined by physico- chemical methods and by electron microscopy. A variety of repressor ligands will be examined for their capacity to bind free repressor and to act as inducers or anti-inducers at the level of the repressor- operator complex. New types of mutants altered either in the structure of the repressor or of the operator will be isolated and characterized in vitro, in order to define the features of the repressor and of the operator which are important for their interaction. (2) The Galactose Operon: The isolation of the gal repressor will be attempted and its properties examined using the methodology developed for the lac repressor. (3) Glucocorticosteroid Regulation: Resistance to glucocorticosteroid induced killing of cells of the immune system can be acquired in two ways, which will be compared by biochemical and genetic methods. The first is by selection in tissue culture of neoplastic cell lines, and the second is by the normal process of differentiation. The cell pairs, resistant and sensitive, derived by each of the two processes will be compared with respect to their binding proteins and "dominance" characteristics in hybrids.